Weppler D, Khan R, Fragulidis G P, Nery J R, Ricordi C, Tzakis A G
University of Miami, Department of Surgery, Florida, USA.
Clin Transpl. 1996:187-201.
The liver transplant program at the University of Miami, established in 1987, was rejuvenated in June 1994 with the addition of new staff and expanded to include all organs of the gastrointestinal tract. Since its inception, 630 patients have been transplanted in the program. During the past 2 years we performed 349 transplants in 318 patients (livers n = 323 in 298 patients, liver + kidneys n = 13, liver + islet n = 10, liver + kidney + islets n = 1, liver + heart n = 10, liver + lung n = 1). These included 4 split-liver, 3 living-related, multiple reduced-sized and one "Domino" liver transplant. We have an active pediatric program and 10% of our transplanted patients are pediatric. Our overall patient and graft survival rates were 81% and 78%, respectively. The intestinal transplant program was launched in August 1994. To date we have performed 22 intestinal transplants, in 9 adults and 13 children. These transplants included 4 isolated intestinal, 11 combined liver-intestinal and 7 multivisceral transplants. Overall patient and graft survival rates were 55% and 50%, respectively. During the past 2 years several studies involving immunosuppressive agents were carried out: 1)Mycophenolate Mofetil (MMF) was used as induction therapy and as rescue therapy in patients with steroid-resistant rejection. Tacrolimus toxicity, and chronic rejection; 2) Neoral was compared with Tacrolimus in patients with Hepatitis C; and 3) MMF was added as triple therapy for the intestinal transplants. We used alpha interferon-2b (alpha-IFN) in hepatitis C positive patients in the early posttransplant period and found that it appears to be a safe drug. There was no increase in rejection in patients receiving alpha-IFN, and patient and graft survival were the same as in our overall patient population. A combination a-IFN with Ribavirin will be undertaken in the near future. The use of Lamivudine in hepatitis B patients was shown to be effective in preventing and treating recurrence of hepatitis B posttransplant. Unmodified donor bone marrow cells (DBMC) were isolated from the vertebral bodies of the same cadaveric liver donors. Donor bone marrow dose, number of cells and/or number (or timing) of infusions were investigated to determine which variables affected the ability of DBMC to engraft in the liver recipient. The long-term benefit of DBMC needs further follow-up. Although, our patient and graft survival for liver transplant recipients is comparable to other large centers nationally and internationally, we still have some challenges to overcome. These include: 1) control and prevention of recurrent HCV, 2) improved treatment for hepatocellular cancer pre- and posttransplant, and 3) treatment and prevention of chronic rejection. Intestinal transplantation remains an even greater challenge. Diagnostic tests to determine intestinal function need further development and although MMF has shown some promise in this field, newer immunosuppressive medications need to be investigated to prevent rejection and avoid over immunosuppression.
迈阿密大学的肝脏移植项目始于1987年,1994年6月通过增加新员工得以重振,并扩大到包括胃肠道的所有器官。自项目启动以来,已有630名患者接受了移植。在过去的两年里,我们为318名患者进行了349例移植手术(298名患者移植肝脏,共323例;298名患者移植肝脏 + 肾脏,共13例;298名患者移植肝脏 + 胰岛,共10例;298名患者移植肝脏 + 肾脏 + 胰岛,共1例;298名患者移植肝脏 + 心脏,共10例;298名患者移植肝脏 + 肺,共1例)。其中包括4例劈离式肝移植、3例活体亲属供肝移植、多例减体积肝移植和1例“多米诺”肝移植。我们有一个活跃的儿科项目,10%的移植患者为儿童。我们的总体患者和移植物存活率分别为81%和78%。肠道移植项目于1994年8月启动。迄今为止,我们已为9名成人和13名儿童进行了22例肠道移植手术。这些移植手术包括4例孤立性肠道移植、11例肝肠联合移植和7例多脏器移植。总体患者和移植物存活率分别为55%和50%。在过去的两年里,我们开展了几项涉及免疫抑制剂的研究:1)霉酚酸酯(MMF)被用作诱导治疗以及对类固醇抵抗性排斥、他克莫司毒性和慢性排斥患者的挽救治疗;2)在丙型肝炎患者中比较了新山地明与他克莫司;3)MMF被添加用于肠道移植的三联治疗。我们在移植后早期对丙型肝炎阳性患者使用了α干扰素-2b(α-IFN),发现它似乎是一种安全的药物。接受α-IFN的患者排斥反应没有增加,患者和移植物存活率与我们的总体患者群体相同。在不久的将来,将开展α-IFN与利巴韦林联合使用的研究。已证明拉米夫定用于乙型肝炎患者可有效预防和治疗移植后乙型肝炎复发。从未经处理的供体骨髓细胞(DBMC)中分离出同一尸体肝脏供体的椎体。研究了供体骨髓剂量、细胞数量和/或输注次数(或时间),以确定哪些变量会影响DBMC在肝脏受体中的植入能力。DBMC的长期益处需要进一步随访。尽管我们肝脏移植受者的患者和移植物存活率与国内和国际其他大型中心相当,但我们仍有一些挑战需要克服。这些挑战包括:1)控制和预防丙型肝炎复发;2)改善移植前后肝细胞癌的治疗;3)治疗和预防慢性排斥。肠道移植仍然是一个更大的挑战。确定肠道功能的诊断测试需要进一步发展,尽管MMF在该领域已显示出一些前景,但需要研究更新的免疫抑制药物以预防排斥并避免过度免疫抑制。